Overlap of highly FDG-avid and FMISO hypoxic tumor subvolumes in patients with head and neck cancer

<b>Background:</b> PET imaging may be used to personalize radiotherapy (RT) by identifying radioresistant tumor subvolumes for RT dose escalation. Using the tracers [¹⁸F]-fluorodeoxyglucose (FDG) and [¹⁸F]-fluoromisonidazole (FMISO), different aspects of tumor biology can be visualized. FDG depicts various biological aspects, e.g., proliferation, glycolysis and hypoxia, while FMISO is more hypoxia specific. In this study, we analyzed size and overlap of volumes based on the two markers for head-and-neck cancer patients (HNSCC). <b>Material and methods:</b> Twenty five HNSCC patients underwent a CT scan, as well as FDG and dynamic FMISO PET/CT prior to definitive radio-chemotherapy in a prospective FMISO dose escalation study. Three PET-based subvolumes of the primary tumor (GTV_prim) were segmented: a highly FDG-avid volume <i>V</i>_FDG, a hypoxic volume on the static FMISO image acquired four hours post tracer injection (<i>V</i>_H) and a retention/perfusion volume (<i>V</i>_M) using pharmacokinetic modeling of dynamic FMISO data. Absolute volumes, overlaps and distances to agreement (DTA) were evaluated. <b>Results:</b> Sizes of PET-based volumes and the GTV_prim are significantly different (GTV_prim&gt;<i>V</i>_FDG&gt;<i>V</i>_H &gt;<i>V</i>_M; <i>p</i> V_H is covered by <i>V</i>_FDG or DTAs are small (mean coverage 74.4%, mean DTA 1.4 mm). Coverage of <i>V</i>_M is less pronounced. With respect to <i>V</i>_FDG and <i>V</i>_H, the mean coverage is 48.7% and 43.1% and the mean DTA is 5.3 mm and 6.3 mm, respectively. For two patients, DTAs were larger than 2 cm. <b>Conclusions:</b> Hypoxic subvolumes from static PET imaging are typically covered by or in close proximity to highly FDG-avid subvolumes. Therefore, dose escalation to FDG positive subvolumes should cover the static hypoxic subvolumes in most patients, with the disadvantage of larger volumes, resulting in a higher risk of dose-limiting toxicity. Coverage of subvolumes from dynamic FMISO PET is less pronounced. Further studies are needed to explore the relevance of mismatches in functional imaging.

<b>背景：</b> 正电子发射断层成像（Positron Emission Tomography, PET）可通过识别放射抵抗性肿瘤亚体积以开展放射治疗（Radiotherapy, RT）剂量递增，从而实现放射治疗的个性化。使用氟代脱氧葡萄糖（[¹⁸F]-fluorodeoxyglucose, FDG）与氟米索硝唑（[¹⁸F]-fluoromisonidazole, FMISO）两种示踪剂，可可视化肿瘤生物学的不同特征：FDG可反映增殖、糖酵解与缺氧等多种生物学过程，而FMISO对缺氧具有更高的特异性。本研究针对头颈鳞癌（Head and Neck Squamous Cell Carcinoma, HNSCC）患者，分析了两种标记物对应的肿瘤亚体积的大小与重叠情况。
<b>材料与方法：</b> 本研究为一项前瞻性FMISO剂量递增研究，共纳入25例HNSCC患者，所有患者在接受根治性放化疗前均完成了CT扫描以及FDG和动态FMISO PET/CT检查。研究人员对原发肿瘤大体肿瘤体积（Gross Tumor Volume_prim, GTV_prim）的3个PET亚体积进行了分割：高FDG摄取体积<i>V</i>_FDG、示踪剂注射4小时后采集的静态FMISO图像上的乏氧体积<i>V</i>_H，以及基于动态FMISO数据药代动力学建模得到的滞留/灌注体积<i>V</i>_M。本研究对上述亚体积的绝对体积、重叠度以及一致性距离（Distance to Agreement, DTA）进行了评估。
<b>结果：</b> PET相关亚体积与GTV_prim的大小存在显著统计学差异，排序为GTV_prim > <i>V</i>_FDG > <i>V</i>_H > <i>V</i>_M；<i>V</i>_H大多被<i>V</i>_FDG覆盖，或二者一致性距离较小（平均覆盖度74.4%，平均DTA为1.4mm）。<i>V</i>_M的覆盖度则相对较低。针对<i>V</i>_FDG与<i>V</i>_H，平均覆盖度分别为48.7%与43.1%，平均DTA分别为5.3mm与6.3mm。其中2例患者的DTA大于2cm。
<b>结论：</b> 静态PET成像得到的乏氧亚体积通常处于高FDG摄取亚体积的覆盖范围内或与之邻近。因此，对FDG阳性亚体积进行剂量递增时，在大多数患者中可同时覆盖静态乏氧亚体积，但弊端是靶体积更大，会增加剂量限制性毒性的发生风险。动态FMISO PET对应的亚体积覆盖度则相对较低。仍需开展进一步研究以明确功能成像匹配偏差的临床相关性。